Genetic secrets of Alzheimer’s disease revealed – thanks to little pigs

Researchers in Denmark say they have discovered that destroying a specific gene can prevent early Alzheimer’s disease. The test subjects who helped them prove it: a lab-raised car to drive the world’s tiniest domestic pig.

in cooperation Between the Department of Biomedicine and the Department of Clinical Medicine at Aarhus University, the researchers bred a group of piglets – called Gottingen minipigs – which they hope will allow advanced future studies of the early sequencing of events in Alzheimer’s disease.

For the study, recently published in Cell Reports Medicine, researchers in Denmark used CRISPR gene-editing technology to raise piglets with intentional damage to a specific gene: the SORL1, or Sortilin-1-related receptor, which has been found to be altered in about 2 to 3 percent of cases From Early Alzheimer’s disease disease in humans.

Ellegaard Gottingen Alzheimers CRISPR Research minipigs
Minipigs bred in Göttingen for medical research are helping a team in Denmark decipher Alzheimer’s disease. Photo: minipigs Ellegaard Gottingen

Just like humans with this gene, the researchers hypothesized that pigs are very likely to develop Alzheimer’s disease at a younger age, giving the team more time to study the mysterious early stages of the disease.

The research team’s CRISPR trial worked: All of the Gottingen minipigs showed signs of Alzheimer’s disease before the age of three.

“By following changes over time in pigs, we can better understand early changes in cells,” said lead author of the study Olaf Michael Andersen, professor at Aarhus University and winner of the Alzheimer’s Research Foundation Research Grant 2020.

“Later, these changes lead to irreversible changes in the brain that are the cause of dementia,” he said. “But now we can follow the pigs before they lose their memory, change their behaviour, [etcetera]making it possible to test new drugs that could be used at an early stage to prevent Alzheimer’s disease associated with SORL1.”

SORL1 is one of several genesincluding APP, PS1, PS2, APOE4known to be associated with the development of Alzheimer’s disease. SORL1 was the first specified At Andersen University and colleagues, Aarhus University, in 1996. Attributed to Dr. Philip Schiltens Establishing As a cause of early Alzheimer’s disease in The Lancet in 2021.

“We know from human genetics that when the SORL1 gene is destroyed, we develop Alzheimer’s disease,” Andersen said. We’ve shown that if we knock out this gene in pigs, exactly the earliest changes occur in the brain cells of the animals we dared hope. This makes it possible to find biomarkers that reflect the initial, preclinical stage of the disease.”

Pigs… they’re just like us

Pigs are an example of the effectiveness of using large animals to study neurodegenerative diseases because they have more brains like humans Who have studied often mice and mice.

“Pigs are similar in many ways to humans, which is why this raises the prospects of producing drugs that will work against Alzheimer’s disease,” Andersen said. “It is important to have a working animal model to bridge the gap between research and drug development.”

study from Carleton University in Ottawa He outlined the important role of pigs in the study of neurodegenerative diseases due to the similarity between species. Pigs naturally share tau isoforms, which are known to appear in the brains of people with Alzheimer’s disease, while rodents do not. Humans and pigs also share similar densities of white and Gray matter or unclear in the brain.

Pigs and humans also share similar numbers of serotonin neurons, approximately six to eight times the number of serotonin neurons in mice. Surprisingly, pig brains share a similar gender-specific development as human: female brains in both species experience hippocampal development earlier than male brains. Researchers can use the same Tools on pig brains that they use to study human brains because they are similar in size.

Pigs require more space and resources than rodents in the lab, so using these specially bred piglets is a compromise that allows researchers to tap into pigs’ brains without the need for large, resource-packed nurturing spaces.

Alzheimer's genetics research pigs
“Pigs are similar to humans in many ways, which is why this increases the odds of producing drugs that will work against Alzheimer’s disease. It is important to have a working animal model to bridge the gap between research and drug development.” Professor Olaf Michael Andersen, Alzheimer’s Disease Researcher Photo: minipigs Ellegaard Gottingen

The researchers say their goal is to develop drugs based on studies of Gottingen minipigs. cases of dementia Soar all over the worldAnd drugs don’t catch up.

According to Andersen, these lab pigs could be the answer. “Pigs can be used in the pharmaceutical industry to develop new drugs, and at the same time, this could provide researchers with better possibilities to understand early changes in the brains of people who will later develop Alzheimer’s disease,” he said.

Andersen’s team is currently breeding another set of minipigs, with plans To collect blood for blood plasma biomarkers.

“The best thing is to develop new drugs based on this pig model, and we’re already well ahead of the preparations,” he said.

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